(Seattle Children's Hospital) Expanded Therapeutic Window of Potent Bispecific PD-L1 T Cell Engager with Novel Best-in-Class CD3 Binder

Abstract

Bispecific T cell engagers (TCE) are potent, off the shelf immune modulators that have been hugely successful against hematologic malignancies and are beginning to demonstrate utility in solid tumors. PD-L1 targeting bispecific TCE with an SP34 variant CD3 binder showed exceptionally potent activity against intracranial tumor models in mice. To further expand the potential therapeutic index, we engineered SCRI-6, a novel, high affinity, non-polyreactive CD3 binder, into a next generation PD-L1 TCE and compared the SP34 and SCRI-6 versions for efficacy and tolerability.